Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19)
- Conditions
- COVID-19
- Interventions
- Registration Number
- NCT04380519
- Lead Sponsor
- R-Pharm International, LLC
- Brief Summary
The primary objective of the study was to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study.
- Detailed Description
The study consisted of two phases:
* Pilot phase: the first 189 patients were randomized in three groups to receive OKZ, RPH-104 (63 patients per group), followed by an interim analysis of efficacy and safety data.
* The main phase was the conduct of all procedures prespecified in the protocol. Based on results of interim analysis no changes were made regarding the sample size or primary efficacy endpoint.
For each patient the study included the following periods:
* Screening period for no more than 48 hours before the start of the day of randomization (Day 1). During the screening period, an assessment was performed to determine whether the patient met the eligibility criteria;
* Treatment period lasting from the end of the screening (considered as the beginning of the Day 1) to 23:59 of the Day 1, including randomization of the patients in the treatment groups and then a single administration of the study drug;
* Follow-up period lasting from 00:00 of the Day 2 to 23:59 of the Day 29, including an assessment of the efficacy and safety after administration of the study drug.
Eligible patients were randomized to one of three treatment groups to receive a single subcutaneous injection: RPH-104 80 mg, OKZ 64 mg or placebo in addition to standard care for patients with COVID-19 as per the routine practice in participating facilities. Further, during the term of hospitalization, the clinical observation was performed (Day 1 - Day 15 of the Last Hospitalization Day (LHD), whichever comes first). This was followed by a follow-up period from the from Day 15 or LHD (whichever comes first) to Day 29.
Standard COVID-19 therapy, as per the institution routine practice, was permitted during the study, except the prohibited protocol medication (during the whole period of the study) and tocilizumab and sarilumab (during the first 24 hours after the study treatment administration).
In the absence of positive dynamics in the patient's condition (as per Investigator's judgement), it was possible to administrate a single dose of tocilizumab or sarilumab (in accordance with the actual recommendations), after the 24 hours from one of the study drug's administration.
On Day 15 primary endpoint of patient's clinical status (response to the study therapy) was assessed. The response to the therapy was considered as improvement of the patient's clinical status by at least 1 point on a 6-point COVID-19 scale in the absence of tocilizumab or sarilumab administration.
The last patient's visit in the study was the visit on Day 29. If the patient was discharged from the hospital earlier than Day 15 or Day 29, patient's clinical status at these visits were assessed by phone call.
The total expected duration of the study for each patient was not more than 31 days, including 48 hours of screening, 1 day of the study drug administration and 28 days of observation.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 372
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RPH -104 80 mg RPH-104 80 mg Subject randomized to receive subcutaneous single injection of 2 ml solution of RPH-104 on Day 1, in addition to standard therapy Olokizumab 64 mg Olokizumab 64 mg Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Olokizumab on Day 1, in addition to standard therapy Placebo Placebo Subject randomized to receive subcutaneous single injection of 2 ml solution of Placebo on Day 1, in addition to standard therapy
- Primary Outcome Measures
Name Time Method Proportion of Responders in Each Treatment Group Day 15 Proportion of patients, responded to the study therapy, in each of the treatment groups.
A responder is a patient who has not received tocilizumab or sarilumab and who has a clinical status improvement of ≥1 point on the 6-point COVID-19 scale (where 1 is the most favorable outcome and 6 is the most undesirable outcome) 15 days after the administration of the study drug:
1. Not hospitalized, no activity limitations.
2. Not hospitalized, limited activity.
3. Hospitalized, not requiring supplemental oxygen.
4. Hospitalized, supplemental oxygen with independent breathing.
5. Hospitalized; mechanical ventilation (invasive/non-invasive) or Extracorporeal membrane oxygenation (ECMO).
6. Death.
- Secondary Outcome Measures
Name Time Method Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale from Day 2 until Day 15, Day 29 Changes of patients' clinical status on a 6 points ordinal scale (where 1 was the most favorable outcome and 6 was the most undesirable outcome) over time.
The 6-point ordinal scale included the following categories:
1. Not hospitalized, no activity limitations.
2. Not hospitalized, limited activity.
3. Hospitalized, not requiring supplemental oxygen.
4. Hospitalized, supplemental oxygen, with independent breathing.
5. Hospitalized, mechanical ventilation (invasive/non-invasive) or ECMO.
6. Death.The Proportion of Patients With an Improvement in Clinical Status by 2 or More Points on the 6-point Ordinal Scale During the Study With no Use of Tocilizumab or Sarilumab Day 29 The proportion of patients with an improvement in clinical status by 2 or more points on the 6-point ordinal scale (where 1 was the most favorable outcome and 6 was the most undesirable outcome) during the study with no use of tocilizumab or sarilumab.
The 6-point ordinal scale included the following categories:
1. Not hospitalized, no activity limitations.
2. Not hospitalized, limited activity.
3. Hospitalized, not requiring supplemental oxygen.
4. Hospitalized, supplemental oxygen, with independent breathing.
5. Hospitalized, mechanical ventilation (invasive/non-invasive) or ECMO.
6. Death.The Proportion of Patients Who Received Tocilizumab or Sarilumab for COVID-19 During the Study from Day 2 until the Day 29 The proportion of patients who received tocilizumab or sarilumab for COVID-19 during the study
Mortality Rate During the Study from Day 1 until Day 29 Mortality rate over the follow-up period of the study
Trial Locations
- Locations (16)
State Budget Healthcare Institution "City Clinical Hospital № 15 named after O.M. Filatov" of Moscow City Healthcare Department
🇷🇺Moscow, Russian Federation
Moscow State Budget Institution of Healthcare "Scientific Research Institute of Emergency Medicine named after N.V. Sklifosovsky of Moscow Department of Healthcare"
🇷🇺Moscow, Russian Federation
Saint-Petersburg State Budget Institution of Healthcare "City Hospital №40"
🇷🇺Saint Petersburg, Russian Federation
Federal State Budgetary Educational Institution of Higher Education "Volga Research Medical University" of the Ministry of Health of the Russian Federation
🇷🇺Nizhniy Novgorod, Russian Federation
Budgetary Health Institution Voronezh Regional Clinical Hospital №1
🇷🇺Voronezh, Russian Federation
Federal State Budgetary Institution "Federal Center for Cerebrovascular Pathology and Stroke" of the Ministry of Health of the Russian Federation
🇷🇺Moscow, Russian Federation
Federal State Autonomous Education Institution of High Education the First Moscow State Medical University named after I.M. Sechenov of Ministry of Healthcare of the Russian Federation (Sechenov University)
🇷🇺Moscow, Russian Federation
Federal Budgetary State Healthcare Institution "National Medical Research Center named after B.A. Almazov"
🇷🇺Saint-Petersburg, Russian Federation
Private healthcare institution "Clinical Hospital" Russian Railways-Medicine named after N. A. Semashko"
🇷🇺Moscow, Russian Federation
Federal State Budget Institution "National Medicine Research Center on Cardiology" By Ministry of Healthcare of Russian Federation
🇷🇺Moscow, Russian Federation
State budgetary healthcare institution City Clinical Hospital named after S.I. Spasokukotsky Department of Health of the city of Moscow City Clinical Hospital No. 50
🇷🇺Moscow, Russian Federation
Federal State Autonomous Education Insitution of High Education the First Moscow State Medical University named after I.M. Sechenov of Ministry of Healthcare of Russian Federation (Sechenov University)
🇷🇺Moscow, Russian Federation
State Budget Institution of Healthcare "City Clinical Hospital #52", Moscow City Healthcare Department
🇷🇺Moscow, Russian Federation
State Budget Healthcare Institution of Yaroslavl Region "Yaroslavl Region Clinical Hospital of War Veterans"
🇷🇺Yaroslavl, Russian Federation
Federal State Budgetary Institution "Central Clinical Hospital with Polyclinic" of Administrative Directorate of the President of the Russian Federation
🇷🇺Moscow, Russian Federation
АО "State Company "Medsi" based on Clinical Hospital №1"
🇷🇺Moscow, Russian Federation